T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma

• Type of Material: Article
• Authors: Xuefeng Wang, H Lee Moffitt Cancer Center and Research Center Inc; Jameel Muzaffar, H Lee Moffitt Cancer Center and Research Center Inc; Kedar Kirtane, H Lee Moffitt Cancer Center and Research Center Inc; Feifei Song, H Lee Moffitt Cancer Center and Research Center Inc; Matthew Johnson, H Lee Moffitt Cancer Center and Research Center Inc; Michael J Schell, H Lee Moffitt Cancer Center and Research Center Inc; Jiannong Li, H Lee Moffitt Cancer Center and Research Center Inc; Sean J Yoder, H Lee Moffitt Cancer Center and Research Center Inc; Jose R Conejo-Garcia, H Lee Moffitt Cancer Center and Research Center Inc; Jose A Guevara-Patino, H Lee Moffitt Cancer Center and Research Center Inc; Marcelo Bonomi, Ohio State University; Priyanka Bhateja, Ohio State University; James W Rocco, Ohio State University; Conor Steuer, Emory University; Nabil Saba, Emory University; Christine H Chung, H Lee Moffitt Cancer Center and Research Center Inc
• Language: English
• Date: 2022-06-01
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jitc-2022-004512
• Title of Journal or Parent Work: JOURNAL FOR IMMUNOTHERAPY OF CANCER
• Volume: 10
• Issue: 6
• Grant/Funding Information: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Grant Sponsor or the H. Lee Moffitt Cancer Center & Research Institute.; It is also supported in part by a National Institute of Health grant, R01DE030493; and Moffitt’s Biostatistics and Bioinformatics Shared Resources, Tissue Core, and Genomics Core Facilities at the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center (P30-CA076292).; This work has been supported in part by the James and Esther King Biomedical Research Grant (7JK02) and Lilly. Bristol Myers Squibb provided nivolumab.
• Keywords: Oncology; Life Sciences & Biomedicine; Immunology; NATURAL-KILLER; Science & Technology; immunotherapy; head and neck neoplasms; IMMUNITY
• Research Categories: Biology, Biostatistics; Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

Background T cell receptor (TCR) signaling profile is a fundamental property that underpins both adaptive and innate immunity in the host. Despite its potential clinical relevance, the TCR repertoire in peripheral blood has not been thoroughly explored for its value as an immunotherapy efficacy biomarker in head and neck squamous cell carcinoma (HNSCC). The purpose of the present study is to characterize and compare the TCR repertoire in peripheral blood mononuclear cells (PBMC) from patients with HNSCC treated with the combination of cetuximab and nivolumab. Methods We used the immunoSEQ assay to sequence the TCR beta (TCR-B) chain repertoire from serially obtained PBMC at baseline and during the treatments from a total of 41 patients who received the combination (NCT03370276). Key TCR repertoire metrics, including diversity and clonality, were calculated and compared between patients with different therapy responses and clinical characteristics (eg, human papillomavirus (HPV) status and smoking history). Patient survival outcomes were compared according to patient groups stratified by the TCR-B clonotyping. To confirm the observed patterns in TCR spectrum, samples from patients who achieved complete response (CR) and partial response (PR) were further profiled with the immunoSEQ deep resolution assay. Results Our data indicated that the patients who achieved CR and PR had an increased TCR sequence diversity in their baseline samples, this tendency being more pronounced in HPV-negative patients or those with a smoking history. Notably, the CR/PR group had the lowest proportion of patients with oligoclonal TCR clones (2 out of 8 patients), followed by the stable disease group (9 out of 20 patients) and lastly the progressive disease group (7 out of 10 patients). An overall trend toward favorable patient survival was also observed in the polyclonal group. Finally, we reported the shared TCR clones across patients within the same response group, as well as the shared clones by aligning immunoSEQ reads with TCR data retrieved from The Cancer Genome Atlas- head and neck squamous cell carcinoma (TCGA-HNSC) cohort. Conclusions Our data suggest that, despite the great clinical heterogeneity of HNSCC and the limited responders in the present cohort, the peripheral TCR repertoires from pretreatment PBMC may be developed as biomarkers for the benefit of immunotherapy in HNSCC.